饮茶与胆道癌胆石症关系的全人群病例对照研究

目的 探讨饮茶与胆道癌和胆石症的关系。方法 采用全人群病例对照研究。研究对象为上海市区新发胆道癌患者627例,包括胆囊癌368例,肝外胆管癌191例和壶腹癌68例;按年龄（每5岁1组）频数配对的对照人群959人;同时收集胆石症患者1037例。采用非条件Logistic回归模型,分析饮茶与胆道癌、胆石症的关系。结果 与不饮茶者比较,女性胆囊癌、肝外胆管癌和胆石症组中现仍饮茶者的调整OR分别为0．57（95％CI：0．34～0．96）、0．53（95％CI：0．27～1．03）和0．71（95％CI：0．51～0．99）,肝外胆管癌OR值随饮茶年龄的提前及饮茶年限的增加而降低,趋势检验达到显著性水平。男性胆囊癌、肝外胆管癌和胆石症组OR均〈1,但尚无统计学意义。结论 饮茶对女性胆囊癌、肝外胆管癌可能具有保护作用,这一保护作用不依赖于胆石症而具有独立性。     

既往疾病史和胆道癌关系的全人群病例对照研究

目的　研究分析既往疾病史和胆道癌 (包括胆囊癌、肝外胆管癌和壶腹部癌 )的关系。方法　自 1997年 6月～ 2 0 0 1年 5月 ,在上海市区开展了一项大规模的基于全人群的胆道癌的病例对照研究 ,共收集、调查了 6 6 4例胆道癌新病例和 894例人群对照。结果　研究发现既往有胆囊炎疾病史者患胆囊癌、肝外胆管癌的危险性升高 ,调整的比数比分别为 2 .2 (95 %CI =1.3～ 3.6 )和 1.9(95 %CI=1.0～ 3.3)。糖尿病患者患胆囊癌的危险性增加 ,调整的比数比为 1.5 (95 %CI=0 .9～ 2 .5 ) ,在非胆结石者中调整的比数比为 2 .0 (95 %CI=0 .9～ 4 .5 ) ;此外 ,研究还发现肝硬化者患肝外胆管癌的危险性明显增加 ,调整的比数比为 3.0 (95 %CI=1.0～ 9.1) ,在非胆结石者中调整的比数比为 4 .9(95 %CI=1.2～ 19.8)。结论　该项研究为论证胆囊炎症增加患胆道癌的危险性提供了依据 ,研究还提示糖尿病和肝硬化分别提高患胆囊癌和肝外胆管癌的危险性。     

CCK及CCKAR基因多态性与胆道癌及胆石症遗传易感性的关系

目的:研究胆囊收缩素(cholecystokinin,CCK)rs747455位点及胆囊收缩素A受体(cholecystokinin A receptor,CCKAR )rs1800856位点的基因多态性与上海市区人群胆道癌及胆石症易感性的关系。方法:采用全人群病例-对照研究的方法,运用实时荧光定量PCR系统对253例胆囊癌、133例肝外胆管癌、53例壶腹癌和440例胆石症患者以及445名正常对照进行CCK rs747455及CCKAR rs1800856位点基因型分析。结果:无胆石个体中携带CCK rs747455位点CT基因型者较携带CC基因型者罹患壶腹癌的风险降低,其比值比(odds ratio,OR)=0.31,95%可信区间(confidence interval,CI)为0.10～0.96,经过Bonferroni校正后此差异仍有统计学意义(P=0.042);饮酒个体中携带rs747455位点TT基因型或CT基因型者较携带CC基因型者罹患胆石症的概率增加(OR=2.81, 95%CI:1.08～7.29;OR=2.93, 95%CI:1.03～8.33),但经过Bonferroni校正后差异无统计学意义(P=0.061)。在CCKAR rs1800856位点的分层分析中未发现该位点与胆道癌及胆石症有显著相关性。结论:CCK基因rs747455位点可能与中国上海人群胆道癌及胆石症的发生相关。     

DNA修复基因XPD单核苷酸多态与胆道癌遗传易感性

目的:研究核苷酸切除修复基因XPDAsp312Asn位点以及Lys751Gln位点多态与上海市区人群胆道癌风险的关系。方法:采用全人群病例-对照研究的方法运用PCR-RFLP对443名胆道癌患者和448名正常对照进行基因型分析。比较各基因型在病例与对照中分布频率的差异,并探讨基因、环境因素在胆道癌发生过程中的作用。结果:与携带XPD 751Lys/Lys基因型者比较,携带Gln/Gln基因型者罹患胆道癌的风险显著增加(校正OR=6.32;95%CI=1.16~34.53)。按解剖部位分析显示,风险增高只限于壶腹部癌(校正的OR=13.17;95%CI=1.71~101.38)。携带312Asn/Asn基因型者罹患壶腹部癌的风险显著高于携带Asp/Asp基因型者(校正后OR=20.09;95%CI=1.13~357.99)。在不伴有胆石症人群中,751Gln/Gln基因型携带者罹患胆道癌风险增加(校正后OR=5.92;95%CI=1.05~33.36),提示在不伴有胆石症人群中,遗传因素可能是发生胆道癌的影响因素。而在饮酒人群中携带751Lys/Gln或Gln/Gln基因型者较携带Lys/Lys基因型者患胆道癌风险增加约3倍。结论:XPD 312Asn等位基因以及751Gln等位基因可能是中国上海地区人群胆道癌尤其是壶腹部癌风险的遗传易感因素。     

核苷酸切除修复基因和谷胱甘肽-S-转移酶基因多态与胆道癌风险关系的研究

目的:研究核苷酸切除修复基因XPA、XPC、XPD、XPG及Ⅱ相代谢酶基因GSTM1、GSTT1多态与上海市市区人群胆道癌风险的关系.方法:采用全人群病例-对照研究的方法,运用聚合酶链反应-限制性片段长度多态(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)的方法对443例胆道癌患者和845例正常对照进行基因型分析.比较各基因型在病例与对照中分布频率的差异,并探讨其与胆道癌之间的关系.结果:XPD exon10-Asp312Asn和exon23-Lys751Gln多态位点的频率分布在壶腹癌病例和对照之间的差异有统计学意义(P<0.05),调整了年龄、性别、吸烟、胆石症和高血压后,证实Asn/Asn和Gln/Gln基因型可能增加壶腹癌的危险, 比值比(odds ratio,OR)分别为32.03和9.33,且趋势检验有统计学意义.未发现其他修复基因多态位点与胆道癌有关联.分层分析显示,GSTM1缺失型可增加女性胆囊癌发生的危险,OR=1.73(95%可信区间:1.06～2.82).在胆道癌的发生中,GSTM1与部分修复基因存在联合作用.结论:XPD exon10-Asn/Asn基因型和exon23 Gln/Gln基因型可能与壶腹癌的危险性有关.GSTM1缺失型可能增加女性胆囊癌发生的危险,且GSTM1基因型与部分修复基因之间可能存在联合作用.     

上海市胆道癌病理形态特征的初步观察:附487例分析

目的研究上海市区居民胆道癌病理形态特征和鉴别诊断.方法自1997年6月～2001年5月在上海市区开展基于全人群的胆道癌病例-对照研究,总共收集病理切片1 228例,包括胆道癌487例(其中胆囊癌322例,肝外胆管癌105例和壶腹癌60例),胆道结石和胆囊炎对照病例721例,胆道腺瘤20例,由中、美资深病理医师复查,按世界卫生组织1991年胆囊和肝外胆管肿瘤组织学分型进行分类.结果病理标本以切除标本为主,肿瘤大小为多数小于4 cm,组织学类型中70%以上为腺癌,肿瘤组织学分级以高分化和中分化占绝大多数,TNM分期中0～Ⅱ期的胆囊癌和肝外胆管癌约占1/3,壶腹癌近2/3.病理复查结果显示诊断过头占1.8%,诊断不足占0.6%,漏诊占0.1%;随访结果显示根治术后的5年生存率:胆囊癌40.7%、肝外胆管癌11.1%和壶腹癌26.9%.结论病理复查可以统一诊断标准,提高确诊率,为全人群病例-对照研究和多学科协作积累经验.     

MTHFR C677T基因型、烟酒嗜好及其相互作用与胃癌

目的研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性及其和烟酒茶嗜好相互作用与胃癌易感性的关系.方法在上消化道癌高发区淮安市进行了一个病例-对照研究(胃癌107例,人群对照200例),调查研究对象的生活习惯,采用PCR-RFLP技术检测研究对象的MTHFR基因型.结果①胃癌组中MTHFR变异型等位基因携带者的比例为79.4%,显著高于对照组的68.5%(x2=4.15,P=0.0416).MTHFR变异型等位基因携带者发生胃癌的危险性显著升高(OR=1.78,95%CI0.99～3.22;性别、年龄吸烟和饮酒习惯调整OR=1.79,95%CI1.01～3.19).②与携带MTHFR野生基因型的不吸烟者相比,携带变异型基因且伴有吸烟习惯者发生胃癌的OR为7.82(95%CI2.43～25.19),伴有经常饮酒的习惯者发生胃癌的OR为2.87(95%CI1.28～6.47).与不吸烟、不经常饮酒的野生型MTHFR基因携带者相比,伴有吸烟和经常饮酒习惯的变异型基因携带者发生胃癌的OR为8.67(95%CI2.12～40.94).结论MTHFRC677T变异型基因型与胃癌的易感性有关;吸烟和饮酒与MTHFR变异基因型在胃癌发生中有明显的协同作用.调查生活习惯同时检测MTHFR基因型有助于胃癌高危人群和个体的筛选.     

饮酒与膀胱癌关系的全人群病例对照研究

目的探讨饮酒与膀胱癌发生的关系。方法采用全人群为基础的病例对照研究,共调查1996年1月1日~1998年12月31日期间确诊的上海市区膀胱癌新发病例608例,健康人群对照607例。采用非条件logistic回归分析,调整吸烟等可能的混杂因素,以估计饮酒对膀胱癌发生的危险度及其95%可信区间。结果与不饮酒者相比,男、女性饮酒者患膀胱癌相对危险度分别是1.22(95%CI0.94~1.59)、0.50(95%CI0.13~1.90)。男性随总酒精摄入量增加患膀胱癌的危险有增加趋势,OR值分别为1.10(1~80g/d)和1.56(>80g/d)(趋势检验P=0.043)。男性总酒精摄入量与饮酒年限的联合作用分析表明,与不饮酒者相比,总酒精摄入量超过80g/d、饮酒年限超过40年者患膀胱癌危险度为2.11(95%CI1.11~4.01)。将饮酒分3层、吸烟分4层进行男性饮酒与吸烟的联合作用分析,结果显示总酒精摄入量>80g/d且吸烟≥35包年者的OR值为2.78(95%CI1.46~5.28)。未发现各饮酒种类与男性膀胱癌有显著关联。在不吸烟男性组中的分析显示,饮酒习惯的OR值均没有统计学意义。结论饮酒可能与男性膀胱癌有一定联系,但作用较弱,似乎主要表现为对吸烟男性的作用。     

p53codon72单核苷酸多态性与肝细胞癌发病风险的关系

[目的]探讨广西地区p53基因codon72单核苷酸多态性(SNP)与肝细胞癌(HCC)发病风险的关系。[方法]采用TaqMan MGB探针等位基因分型技术对985例肝癌病例和相匹配的992例非肿瘤对照的p53 codon72(Arg>Pro,rs1042522)基因型进行检测,并分析该SNP与肝癌发病风险的关系。[结果]p53 codon72多态性与肝癌发病风险之间无统计学关联(Arg/Pro:校正OR=1.15,95%CI:0.83～1.59;Pro/Pro:校正OR=1.16,95%CI:0.80～1.68;Arg/Pro+Pro/Pro:校正OR=1.15,95%CI:0.85～1.57)。按是否吸烟、饮酒、HBV和HCV感染分层分析,亦未发现p53 codon72多态性与肝癌发病风险有关。但基因—环境交互作用显示,该基因多态性与吸烟、饮酒和HBV感染存在交互作用,OR值分别为2.42(95%CI:1.47～3.97)、2.96(95%CI:1.82～4.80)和62.74(95%CI:34.39～114.46)。[结论]p53codon72的单独效应可能与肝癌易感性无关联,但该SNP与吸烟、饮酒和HBV感染存在基因—环境交互作用,增加肝癌的发病风险。     

饮茶与牙龈癌发病关系的病例对照研究北大核心CSCD

目的探讨饮茶对牙龈癌发病的影响。方法采用病例对照的研究方法,病例组为2 0 1 0年1 2月—2 0 1 6年3月经病理确诊的牙龈癌新发病例1 2 1例,同期经性别、年龄成组匹配,选取医院体检人群及社区健康人群363例作对照。应用非条件Logistic回归模型计算饮茶及其相关变量与牙龈癌发病风险的调整比值比(OR)及其95%置信区间(CI)并进行相乘交互作用分析。结果饮茶可降低牙龈癌的发病风险(OR=0.51,95%CI:0.29~0.90);进一步分析发现随着每日饮茶量的增加、饮茶年限的延长,牙龈癌的发病风险也随之降低(均Ptrend<0.05);此外饮茶年龄≥25岁、饮茶浓度适中、饮温茶以及饮绿茶和乌龙茶也可降低牙龈癌的发病风险。分层分析结果发现与吸烟者相比,在非吸烟者中饮茶的保护作用更加显著(OR=0.40,95%CI:0.1 7~0.9 6),在非饮酒和饮酒者中饮茶的保护作用差异则没有统计学意义。交互作用结果并未发现吸烟与饮茶,饮酒与饮茶之间存在相乘交互作用。结论饮茶是牙龈癌发病的保护因素,且每日饮茶量、饮茶年限与牙龈癌发病风险之间呈剂量反应关系。     

血脂水平与胆道癌和胆石症关系的病例对照研究

目的：探讨血脂水平与胆道癌、胆石症的关系。方法：采用全人群病例对照研究方法，对上海市区462例胆道癌、982例胆石症和808例人群对照进行六项血脂指标的检测，采用多样本比较的秩和检验方法分析血脂水平与胆道癌和胆石症的关系。结果：男性胆石症层中，胆道癌患者TG的含量高于胆石症患者和人群对照；且各部位胆石症和胆道癌患者HDL的含量均低于人群对照。男性非胆石症层中，胆道癌患者TG和ApoB的含量显著高于人群对照，而TC、HDL、LDL和ApoA的水平则低于人群对照。在女性胆石症层中。胆道癌、胆石症患者和人群对照HDL、ApoA的平均含量由高到低分别为人群对照、胆石症和胆道癌患者。女性非胆石症层中，胆道癌患者HDL和ApoA的平均含量均显著低于人群对照。结论：男女性胆道癌和胆石症患者都存在脂质代谢异常，胆道癌患者TG水平高于对照和胆石症患者．而HDL水平则低于对照和胆石症患者。     

K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: a population-based study in China.

PURPOSE: The genetic alterations in biliary tract cancer and clinicopathological associations have not been studied in large population-based studies. Experimental Design: We evaluated genetic alterations such as K-ras mutation, p53 overexpression, microsatellite instability (MSI), and alterations of the polyadenine tract present in the transforming growth factor beta receptor type II (TGFbetaRII) gene in 126 biliary tract cancers: 75 gallbladder cancers, 33 bile duct cancers, and 18 ampullary cancers. These genetic alterations were compared with patient demographics and clinicopathological characteristics of the tumors. RESULTS: Mutation of the K-ras gene was present in 18 of 126 (14.3%) biliary tract cancers. K-ras mutation was present in 11 of 18 (61.1%) ampullary cancers, 5 of 33 (15.2%) bile duct cancers, and 2 of 75 (2.7%) gallbladder cancers (P = 0.000001). The mean survival of patients who had bile duct carcinomas with K-ras mutation was 3.0 +/- 2.2 months compared with 15.5 +/- 12.5 months for those without mutation (P = 0.03) but was not different for other tumor sites. p53 overexpression was present in 34 of 123 (27.6%) cancers. MSI-high (allelic shifts in 40% or more loci or alteration of the TGFbetaRII gene) was present in 4 of 126 (3.2%) biliary tract cancers without hereditary nonpolyposis colorectal cancer. MSI-high was more common in mucinous adenocarcinomas (P = 0.006) and in patients with early age of onset of cancer (P = 0.04). CONCLUSIONS: The genetic alterations in biliary tract cancers are dependent on the tumor subsite, histology, and age of onset and are associated with prognosis.     

Double cancer of gall bladder and bile duct not associated with anomalous junction of the pancreaticobiliary duct system

BACKGROUND: Simultaneous double cancers of the biliary tract are rare. Most of them are thought to be associated with pancreaticobiliary maljunction (PBM); however, the characteristics of tumours without PBM are still unclear. METHODS: Histology, immunoreactivity with carcinoembryonic antigen, carbohydrate antigen 19-9 and p53 and mutations in the K-ras gene were examined in tumours resected from cases of simultaneous double cancers of the biliary tract. RESULTS: Four cases of simultaneous double cancers of the biliary tract were identified among 108 patients with biliary tract cancer (3.7%). None of the four cases associated with PBM, and the results of histological, immunohistochemical and genetic examinations differed between the bile duct and gall bladder cancers in each case. CONCLUSION: Even when they do not associate with PBM, double cancers in the biliary tract are more likely to be the result of multicentric development.     

Medical history and the risk of biliary tract cancers in Shanghai, China: implications for a role of inflammation

Several lines of evidence suggest that inflammation may play a role in the etiology of biliary tract cancers. To examine further the role of inflammation, we evaluated the associations between self-reported inflammatory-related medical conditions and the risk of biliary tract cancers in a population-based case-control study in Shanghai, China. Our analysis included 368 gallbladder cancer cases, 191 bile duct cancer cases, 68 ampulla of Vater cancer cases, and 959 healthy subjects. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for biliary tract cancers in relation to six inflammation-related conditions. Gallbladder cancer was significantly associated with cholecystitis occurring at least 5 years prior to interview (OR = 1.7, 95% CI 1.1-2.9). Even though biliary stones did not significantly modify the associations between cholecystitis and gallbladder cancer, 90% of the gallbladder cancer cases with cholecystitis also had biliary stones, indicating that stones likely play an important role in the link between cholecystitis and gallbladder cancer. Among subjects who smoked and drank alcohol, a history of gastric (OR = 4.3, 95% CI 1.2-15.0) or duodenal ulcers (OR = 3.7, 1.2-12.0) was associated with an excess risk of gallbladder cancer. Although the mechanisms are unclear, our results further support the role for inflammation in the etiology of biliary tract cancers.     

Beta-catenin mutations in biliary tract cancers: a population-based study in China

beta-Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the beta-catenin gene, at the phosphorylation sites for ubiquitination and degradation of beta-catenin, are present in a variety of cancers. Because alterations of the adenomatous polyposis coli (APC) gene are present in biliary tract cancers and the APC protein modulates levels of beta-catenin, we evaluated the role of beta-catenin in biliary tract cancer by sequencing the third exon of the beta-catenin gene among 107 biliary tract cancers and 7 gallbladder adenomas from a population-based study in CHINA: Point mutations of serine or threonine phosphorylation sites in exon 3 of beta-catenin were present in 8 of 107 (7.5%) biliary tract cancers and 4 of 7 (57.1%) gallbladder adenomas. Mutations of beta-catenin were more frequent in ampullary and gallbladder carcinomas than in bile duct carcinomas (P = 0.04) and in papillary adenocarcinomas than other histological types of carcinomas (P = 0.02). These results suggest that the molecular pathways of biliary tract neoplasms vary by anatomical subsite and histological subtype.     

Family history of gallstones and the risk of biliary tract cancer and gallstones: a population-based study in Shanghai, China

Cancers of the biliary tract arise from the gallbladder, extrahepatic bile ducts and ampulla of Vater. Although relatively uncommon, the incidence of biliary tract cancer rose more than 100% in Shanghai, China between 1972 and 1994. Gallstones are the predominant risk factor for biliary tract cancers, with over 60% of the cancer cases having gallstones. A familial tendency to gallstones has been reported and may elevate the risk of gallbladder cancer further. As part of a large population-based case-control study of biliary tract cancers in Shanghai, China, we examined the association between a family history of gallstones and biliary tract cancers as well as biliary stones. A total of 627 biliary tract cancers (368 gallbladder, 191 bile duct, 68 ampulla of Vater), 1,037 biliary stone cases (774 gallbladder, 263 bile duct) and 959 healthy subjects randomly selected from the population were included in this study. Information on family history of gallstones among first-degree relatives (i.e., parents, siblings, offspring) was obtained through a self-reported history during in-person interviews. A family history of gallstones was associated with increased risks of biliary stones [odds ratio (OR) = 2.8, 95% confidence interval (CI) = 2.1-3.8], gallbladder cancer (OR = 2.1, 95% CI = 1.4-3.3) and bile duct cancer (OR = 1.5, 95% CI = 0.9-2.5), after adjustment for age, gender, marital status, education, smoking, alcohol drinking and body mass index. For gallbladder cancer, subjects with gallstones but without a family history of gallstones had a 21-fold risk (95% CI 14.8-30.1), while those with both gallstones and a positive family history had a 57-fold risk (95% CI 32.0-110.5). Significant risks for gallbladder cancer persisted after additional adjustment for gallstones, and when the analysis was restricted to subjects with first-degree relatives whose gallstones were treated with cholecystectomy. The significant associations with a family history of gallstones were seen for all first-degree relatives, including parents, siblings and offspring, but not spouses. This large population-based study not only supports the role of gallstones in biliary carcinogenesis but also suggests that the underlying genetic or lifestyle determinants of stones within families contribute to the risk of biliary tract cancer.     

Tea drinking and the risk of biliary tract cancers and biliary stones: a population-based case-control study in Shanghai, China

Biliary tract cancers, encompassing tumors of the gallbladder, extrahepatic bile ducts and ampulla of Vater, are rare but highly fatal malignancies. Apart from gallstones, etiologic factors for biliary tract cancer are not clearly defined. Several epidemiologic studies have suggested that consumption of tea, especially green tea, is protective against a variety of cancers, including gastrointestinal malignancies. As part of a large population-based case-control study of biliary tract disease in Shanghai, China, we evaluated the effects of tea consumption on the risk of biliary tract cancers and biliary stones. The study included 627 incident cases with biliary tract cancer, 1,037 cases with biliary stones and 959 randomly selected controls. Study subjects were interviewed to ascertain data on demographic, medical and dietary factors, including tea consumption. Forty-one percent of the controls were ever tea drinkers, defined as those who consumed at least 1 cup of tea per day for at least 6 months. After adjustment for age, education and body mass index, among women, ever tea drinkers had significantly reduced risks of biliary stones (OR = 0.73, 95% CI = 0.54-0.98) and gallbladder cancer (OR = 0.56, 95% CI = 0.38-0.83). The inverse relationship between tea consumption and gallbladder cancer risk was independent of gallstone disease. Among men, tea drinkers were more likely to be cigarette smokers, and the risk estimates were generally below 1.0, but were not statistically significant. Further studies are needed to confirm these results in other populations and clarify the hormonal and other mechanisms that may be involved.     

胆道恶性肿瘤的免疫治疗进展

胆道恶性肿瘤是一种恶性程度高、预后极差的消化系统肿瘤.目前化疗是晚期胆道恶性肿瘤的标准一线治疗,但是其治疗效果并不令人满意.近年来免疫治疗发展迅速,特别是免疫检查点抑制剂的推出,在很多实体肿瘤中均取得了良好的疗效.目前胆道系统恶性肿瘤的一些Ⅰ、Ⅱ期临床研究也展现了免疫治疗较好的安全性和有效性.本文就近年来胆道恶性肿瘤方...     

Variants of DNA repair genes and the risk of biliary tract cancers and stones: a population-based study in china

Biliary tract cancers, which encompass tumors of the gallbladder, extrahepatic ducts, and ampulla of Vater, are relatively rare tumors with a high fatality rate. Other than a close link with gallstones, the etiology of biliary tract cancers is poorly understood. We conducted a population-based case-control study in Shanghai, China, to examine whether genetic variants in several DNA repair genes are associated with biliary tract cancers or biliary stones. Genomic DNA from 410 patients with biliary tract cancers (236 gallbladder, 127 bile duct, and 47 ampulla of Vater), 891 patients with biliary stones, and 786 healthy subjects randomly selected from the Shanghai population were genotyped for putative functional single nucleotide polymorphisms in four DNA repair genes (MGMT, RAD23B, CCNH, and XRCC3). Of the five single nucleotide polymorphisms examined, only one (MGMT EX5-25C>T, rs12917) was associated with biliary tract cancer. Independent of gallstones, subjects carrying the CT genotype of the MGMT EX5-25C>T marker had a significantly reduced risk of gallbladder cancer [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.41-0.97; P = 0.02] and nonsignificant reduced risks of bile duct (OR, 0.61; 95% CI, 0.35-1.06) and ampulla of Vater (OR, 0.85; 95% CI, 0.39-1.87) cancers. However, this marker was not associated with biliary stones, and the other markers examined were not significantly associated with either biliary tract cancers or stones. Findings from this population-based study in Shanghai suggest that MGMT gene variants may alter susceptibility to biliary tract cancer, particularly gallbladder cancer. Confirmation in future studies, however, is required.